9-97910041-C-G

Variant names:

• chr9-97910041-C-G
• rs752011184
• NM_016481.5:c.985G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016481.5(TRMO):​c.985G>C​(p.Val329Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V329M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRMO NM_016481.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36
• Publications: 0 publications found

Genes affected

TRMO (HGNC:30967): (tRNA methyltransferase O) Enables tRNA (adenine-N6-)-methyltransferase activity. Involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41754034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016481.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMO	NM_016481.5	MANE Select	c.985G>C	p.Val329Leu	missense	Exon 4 of 5	NP_057565.3
	TRMO	NM_001371657.1		c.985G>C	p.Val329Leu	missense	Exon 4 of 6	NP_001358586.1	Q9BU70
	TRMO	NM_001371658.1		c.985G>C	p.Val329Leu	missense	Exon 4 of 5	NP_001358587.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMO	ENST00000375119.8	TSL:1 MANE Select	c.985G>C	p.Val329Leu	missense	Exon 4 of 5	ENSP00000364260.3	Q9BU70
	TRMO	ENST00000375118.1	TSL:1	c.547G>C	p.Val183Leu	missense	Exon 1 of 2	ENSP00000364259.1	Q5T114
	TRMO	ENST00000864009.1		c.985G>C	p.Val329Leu	missense	Exon 4 of 6	ENSP00000534068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249832 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457796 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724612

African (AFR) AF: 0.00 AC: 0 AN: 33292

American (AMR) AF: 0.00 AC: 0 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109288

Other (OTH) AF: 0.00 AC: 0 AN: 60194

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.56
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.78	T
PhyloP100		3.4
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.069	T
Sift4G	Benign	0.085	T
Polyphen		0.96	D
Vest4		0.55
MutPred		0.35		Gain of sheet (P = 0.1208)
MVP		0.56
MPC		0.45
ClinPred		0.77	D
GERP RS		5.0
Varity_R		0.18
gMVP		0.46
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs752011184; hg19: chr9-100672323;